Method for the production of a metallic substrate having a biocompatible surface and substrate produced using same

ABSTRACT

The invention relates to a method for the production of a metallic substrate having a biocompatible surface and to the substrate that is produced by means of said method. The method comprises treatment of a metal, i.e., Ti, Ti alloys with Al, V, Ta, Nb, Ni, Fe, Mo or mixtures thereof, Ta, Ta alloys with Fe, Al, Cr, stainless steel, with a melt of calcium nitrate and an additional component which is an oxygen salt of Na, K, Li, Mg and mixtures thereof, said treatment being effected at 180-480° C. for 0.1 to 12 hours. A substrate is obtained, wherein the overall layer thickness ranges from 10 to below 1600 nm and the fatigue strength of the substrate is in the same fatigue strength range as that of an untreated substrate at equal number of vibrations N.

The invention relates to a method for the production of a metallicsubstrate having a biocompatible surface and to the substrate that isproduced by means of said method.

A method is known from DE 199 44 970 C1, in which method an implant or asubstrate made of titanium or Ti alloy is treated with a calcium saltmelt to obtain a biocompatible surface. As a result, 1-2 μm layers ofCa₄Ti₃O₁₀ are formed.

The object of the invention is to form thinner layers having highstrength and, at the same time, strong adherence and to make thispossible with metals other than titanium.

According to the invention, the method for the production of a metallicsubstrate with biocompatible surface comprises treatment of a metalselected from the group consisting of titanium; titanium alloys withaluminum, vanadium, tantalum, niobium, nickel, iron, molybdenum ormixtures thereof; tantalum; tantalum alloys with iron, aluminum,chromium or mixtures thereof; stainless steel;

with a melt consisting of calcium nitrate and an additional component,said additional component being selected from the group consisting of anoxygen salt of sodium, potassium, lithium, magnesium and mixturesthereof;said treatment being effected at a temperature ranging from 180 to 480°C. for a period of from 0.1 to 12 hours, the calcium content of the meltbeing at least 20% by weight, relative to the total weight of the melt.

An alloy of titanium with Al and/or V and/or Nb and/or Ni and/or Feand/or Mo is used as preferred titanium alloy.

An alloy of tantalum with iron and/or aluminum and/or chromium is usedas preferred tantalum alloy.

Preferred as additional component is a nitrate or sulfate of Ca, K, Lior Na, with NaNO₃ being advantageous. Particularly preferred is amixture of calcium nitrate and the additional components NaNO₃, KNO₃,LiNO₃ in % by weight: Ca(NO₃)₂ 20 to 95; NaNO₃ 1 to 50; KNO₃ 1 to 50;LiNO₃ 0 to 20.

Advantageously, the temperature in this method ranges from 200 to 480°C., preferably from 250 to 460° C. At such low temperatures, there is noenlargement of the layer thickness, but instead, the latter remainsapproximately constant, altogether resulting in thinner layers thanknown as yet.

The treatment time advantageously ranges from 0.5 to 8 h, preferablyfrom 0.5 to 4 h, particularly from 0.5 to 2 hours.

When adding one or more oxygen salts of sodium, potassium, lithium ormagnesium, it was found that very thin layers of from 5 to 1600 nm,advantageously from 10 to 1000 nm, particularly from 10 to 800 nm, andspecifically from 20 to 450 nm can be obtained at temperaturessubstantially lower than those commonly used so far. The methodaccording to the invention allows coating of such layers not only ontitanium or titanium alloys but also on other types of steel suitablefor biocompatible application, e.g. on stainless steels or on tantalumsteels. With titanium, a layer of CaTiO₃ is formed under the conditionsspecified above.

Tempering as in the well-known process is not required.

The term “oxygen salts” means nitrates, nitrites, sulfates or certainsalts of organic acids such as oxalates or hydroxy succinates.

In the method according to the invention, there is no loss in strengthas a result of the substantial reduction in temperature and the thinnerlayers formed thereby. It was found that e.g. the fatigue strengthvalues of 500-600 MPa at a number of vibrations N of 10⁷ to 10⁵established for untreated titanium alloys are substantially lower forsuch titanium alloys treated according to DE 19944970, being 400 MPa atN=10⁶ and 600 MPa at N=10⁵. In contrast, the materials (titanium,titanium alloys, tantalum, tantalum alloys, stainless steel) treatedaccording to the invention remain in the range of values for therespective untreated materials, thus being clearly superior over theprior art. The fatigue strength was determined using the correspondingtest for unnotched round specimen in accordance with DIN 50113-A.

With titanium or titanium alloys, such as Ti—Al—V, Ti—Ta—Nb, Ti—Ni,Ti—Al—Nb, optionally with Mo and/or Fe, the formation of acalcium-containing reaction layer is particularly advantageous becauseof the accompanying advantageous effects of improving direct bonecontact free of connective tissue.

The oxide layer can form chemical compounds with the calcium to producee.g. calcium titanates. Another advantage is that the method of theinvention modifies the absorptive behavior of proteins on the reactionlayers, allowing more rapid, biologically adapted ingrowth of asubstrate.

By virtue of the method according to the invention, there is less rapidor barely any decomposition of the melt, i.e. the formation of nitrousgases is significantly slowed down. Furthermore, considering thetreatment times involved, a wider temperature interval is available forthe production of the reaction layer on the metal substrate.

The invention is also directed to a metallic substrate having abiocompatible surface, on which substrate, being selected from the groupconsisting of titanium; titanium alloys with aluminum, vanadium,tantalum, niobium, nickel, iron, molybdenum or mixtures thereof;tantalum; tantalum alloys with iron, aluminum, chromium or mixturesthereof; stainless steel;

a reaction layer is formed, consisting of an inner oxide layer facingthe substrate and an outer Ca-containing layer, the overall layerthickness ranging from 10 to below 1600 nm. On its outwardly facingsurface, the outer Ca-containing layer may have Na, K, Li, Mg atoms ormixtures thereof incorporated therein, thereby influencing thesolubility/stability of the implant/bone interface in a lasting fashionand modifying the flux of ions transferred into the body fluid in termsof quality and quantity.

The Ca-containing layer is a reaction layer integrated in the oxidelayer and produced from the reaction of a fused Ca salt with the oxidesurface layer. As a rule, the oxide surface layer on the metal basicbody is increased by the elevated temperature during the process andunder the influence of the salt melt, i.e., the measurable thickness ofthis layer increases. Consequently, this layer is not a coated layersituated on top of the surface, but rather is integrated into the metalsurface (reaction layer). Other elements can be integrated in this layerdown to a specific depth of the layer. Advantageously, the layer is madesignificantly thinner in the substrate according to the invention,ranging from 10 to 1500 nm, particularly from 10 to 800 nm, andspecifically from 20 to 450 nm.

Another feature of the substrate is that the fatigue strength thereof isin the range of the fatigue strength of the untreated substrate.

Preferred is a metallic substrate consisting of titanium or atitanium-containing alloy, wherein the Ca-containing layer consists ofcalcium titanate as major component and the outwardly facing surfacethereof may have Na, K, Li, Mg atoms or mixtures thereof incorporatedtherein. The other metals or metal alloys may contain similarinclusions.

With reference to the examples, the invention will be illustrated inmore detail below. The percentages specified therein are percents byweight (wt.-%).

EXAMPLE 1

A degreased, washed and dried sample of TiAl₆V₄ is kept in a salt meltof calcium nitrate tetrahydrate (74 wt.-%) and sodium nitrate (26 wt.-%)for 4 h at 450° C. Subsequently, it is purified with hot water in anultrasonic bath (10 min) and with dilute hydrochloric acid (1 part ofconc. HCl and 9 parts of water; conc.=concentrated hydrochloric acid, a37% hydrochloric acid being referred to as conc. hydrochloric acid),likewise in an ultrasonic bath (5 min), washed with completely desaltedwater and subsequently with absolute alcohol and dried. Using X-raydiffractometry on thin layers (TF-XRD), formation of calcium titanatewas detected on the surface. The layer thickness of the oxideCa-containing layer was 190 nm, measured using AUGER electronspectroscopy.

EXAMPLE 2

A degreased, washed and dried sample of NiTi is kept in a salt melt ofcalcium nitrate tetrahydrate (74 wt.-%) and sodium nitrate (26 wt.-%)for 4 h at 480° C. Subsequently, it is purified with hot water in anultrasonic bath (10 min) and with dilute hydrochloric acid (1 part of(conc.) HCl and 9 parts of water; also in the following examples),likewise in an ultrasonic bath (5 min), washed with completely desaltedwater and subsequently with absolute alcohol and dried. Using TF-XRD,formation of calcium titanate was detected on the surface.

EXAMPLE 3

A degreased, washed and dried sample of TiAl₆V₄ is kept in a salt meltof calcium nitrate (63 wt.-%), sodium nitrate (17 wt.-%) and potassiumnitrate (23 wt.-%) for 2 h at 400° C. Subsequently, it is purified withhot water in an ultrasonic bath (10 min) and with dilute hydrochloricacid (1 part of HCl+9 parts of water), likewise in an ultrasonic bath (5min), washed with completely desalted water and subsequently withabsolute alcohol and dried. Layer thickness (as in Example 1) 150 nm,measured using AUGER electron spectroscopy. Furthermore, Ca was detectedby means of AUGER electron spectroscopy in the substrate surface down toa depth of 15 nm.

EXAMPLE 4

A degreased, washed and dried sample of high-purity (cp) titanium iskept in a salt melt of calcium nitrate (70 wt.-%), sodium nitrate (12wt.-%), potassium nitrate (12 wt.-%) and lithium nitrate (6 wt.-%) for 2h at 250° C. Subsequently, it is purified with hot water in anultrasonic bath (10 min) and with dilute hydrochloric acid (1 part ofHCl+9 parts of water), likewise in an ultrasonic bath (5 min), washedwith completely desalted water and subsequently with absolute alcoholand dried. The layer thickness (as in Example 1) was 20 nm, measuredusing AUGER electron spectroscopy.

EXAMPLE 5

A degreased, washed and dried sample of implant steel is kept in a saltmelt of calcium nitrate tetrahydrate (74 wt.-%) and sodium nitrate (26wt.-%) for 2 h at 450° C. Subsequently, it is purified with hot water inan ultrasonic bath (10 min) and with dilute hydrochloric acid (1 part ofHCl and 9 parts of water), likewise in an ultrasonic bath (5 min),washed with completely desalted water and subsequently with absolutealcohol and dried.

Using electron spectrometry (ESCA), calcium and sodium were detected inthe layer close to the surface. The layer thickness of the oxideCa-containing layer was 290 nm, measured using AUGER electronspectroscopy.

EXAMPLE 6

A degreased, washed and dried sample of tantalum sheet is kept in a saltmelt of calcium nitrate (70 wt.-%) and sodium nitrate (12 wt.-%) for 4 hat 480° C. Subsequently, it is purified with hot water in an ultrasonicbath (10 min) and with dilute hydrochloric acid (1 part of HCl+9 partsof water), likewise in an ultrasonic bath (5 min), washed withcompletely desalted water and subsequently with absolute alcohol anddried.

Using TF-XRD, formation of calcium tantalate was detected on thesurface. The layer thickness of the oxide Ca-containing layer was 220nm, measured using AUGER electron spectroscopy.

EXAMPLE 7

A degreased, washed and dried sample of TiAl₆V₄ is kept in a salt meltof calcium nitrate (63 wt.-%), sodium nitrate (17 wt.-%) and potassiumnitrate (23 wt.-%) for 25 min at 250° C. Subsequently, it is purifiedwith hot water in an ultrasonic bath (10 min) and with dilutehydrochloric acid (1 part of HCl+9 parts of water), likewise in anultrasonic bath (5 min), washed with completely desalted water andsubsequently with absolute alcohol and dried.

Using AUGER electron spectrometry, Ca was detected in the substratesurface down to a depth of 8 nm.

1-7. (canceled)
 8. A metallic substrate having a biocompatible surface,wherein the substrate, being selected from the group consisting oftitanium; titanium alloys with aluminum, vanadium, tantalum, niobium,nickel, iron, molybdenum or mixtures thereof; tantalum; tantalum alloyswith iron, aluminum, chromium or mixtures thereof, and stainless steel;has a reaction layer formed thereon, consisting of an inner oxide layerfacing the substrate and an outer Ca-containing layer, the overall layerthickness ranging from 10 to below 1600 nm.
 9. The metallic substrateaccording to claim 8, wherein the outer Ca-containing layer hasinclusions of Na, K, Li, Mg atoms or mixtures thereof on its outwardlyfacing surface.
 10. The metallic substrate with biocompatible surfaceaccording to claim 8, wherein the Ca-containing layer is a reactionlayer integrated in the oxide layer and produced from the reaction of afused Ca salt with the oxide layer.
 11. The metallic substrate withbiocompatible surface according to claim 8, wherein the substrateconsists of tantalum or of a tantalum-containing alloy and includes aCa-containing reaction layer, said oxide layer producing a chemicalcompound with said calcium.
 12. The metallic substrate withbiocompatible surface according to claim 9, wherein the inclusions ofsodium, potassium, lithium or mixtures thereof in the outerCa-containing layer are present down to a depth of 20% of the layerthickness of the Ca-containing layer.
 13. The metallic substrateaccording to claim 8, wherein in a substrate selected from the groupconsisting of titanium alloys, tantalum, tantalum alloys, and implantsteels, at least in the outer Ca-containing reaction layer, theconcentration of the additional alloy metals aluminum, vanadium,niobium, nickel, iron, molybdenum, chromium and mixtures thereof islower than that inside the substrate by up to 20% by weight, relative tothe weight of the alloy metal.
 14. The metallic substrate according toclaim 8, wherein the layer thickness ranges from 5 to 1600 nm.
 15. Themetallic substrate according to claim 14, wherein the layer thicknessranges from 10 to 1500 nm.
 16. The metallic substrate according to claim14, wherein the layer thickness ranges from 10 to 800 nm.
 17. Themetallic substrate according to claim 14, wherein the layer thicknessranges from 20 to 450 nm.
 18. The metallic substrate according to claim8, wherein the fatigue strength of the substrate is in the same fatiguestrength range as that of an untreated substrate at equal number ofvibrations N.